Design, Synthesis, And Biological Activity Test Of L-proline And Thiadiazole Derivatives

Alzheimer’s disease(AD) is a chronic neurodegenerative disorder characterized by a progressive loss of cognitive and memory abilities associated with various behavioral disturbances. Nowadays, commercial AD drugs can only release a part of AD patients’ symptoms and have different levels of side effects. Therefore, efforts should still be made to find new AChE inhibitors with high efficency and low side effect by designing and synthesizing new chemical entities.In this paper, 14 new L-proline derivatives were designed and synthesized, furthermore their structures were confirmed by 1H-NMR, MS and IR spectra. The experiments of their inhibiton activity to AChE in vitro were carried out by Ellman method. The experiments result showed that compound 8b had a better AChE inhibition activity to AChE in vitro than others of the 14 compounds, and the IC50 value was to 5.45 μmol/L. The inhibiton activity of 8b to AChE was superior to the compared rivastigmine, and it had little inhibiton activity to BuChE.Meanwhile, 20 new Thiadiazole derivatives were synthesized, and their structures were confirmed by 1H-NMR, MS and IR spectra. The experiments of their inhibiton activity to AChE in vitro were carried out by Ellman method. The experiments result showed that compound 14 b had the best AChE inhibitory activity in the 20 compounds, and the IC50 value was to 15 μmol/L, But its inhibitory activity to AChE was lower than that of the compared rivastigmine.In order to gain the inhibition type of these compounds to AChE, the enzymatic kinetic study was carried out with the most promising compound 8b. The Line weaver-Burk plots showed a mixed type of inhibition.